Transcranial Magnetic Stimulation of Left Dorsolateral Prefrontal Cortex Induces Brain Morphological Changes in Regions Associated with a Treatment Resistant Major Depressive Episode: An Exploratory Analysis

Abstract

Background Repetitive transcranial magnetic stimulation (TMS) is an FDA-approved antidepressant treatment but little is known of its mechanism of action. Specifically, downstream effects of TMS remain to be elucidated. Objective/Hypothesis To identify brain structural changes from TMS treatment of a treatment resistant depressive episode through an exploratory analysis Methods 27 subjects in a DSM-IV current major depressive episode and on a stable medication regimen, had a 3T magnetic resonance T1 structural scan before and after five weeks of standard TMS treatment to the left dorsolateral prefrontal cortex. 27 healthy volunteer (HVs) subjects had the same brain MRI acquisition. Voxel-based morphometry was performed using high dimensional non-linear diffusomorphic anatomical registration (DARTEL). Results Six clusters of grey matter volume (GMV) that were lower in pre-treatment MRI’s of depressed subjects than in HV’s. GMV in four of these regions increased in MDD after TMS treatment by 3.5% to 11.2%. The four brain regions that changed with treatment were centered in the left anterior cingulate cortex, the left insula, the left superior temporal gyrus and the right angular gyrus. Increases in the anterior cingulate GMV with TMS correlated with improvement in depression severity. Conclusions To our knowledge, this is the first study of brain structural changes during TMS treatment of depression. The affected brain areas are involved in cognitive appraisal, decision-making and subjective experience of emotion. These effects may have potential relevance for the antidepressant action of TMS.

Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression

“…Both datasets have been analyzed previously [9,10,31], including a voxel-based morphometry analysis of gray matter density with findings in the rostral anterior cingulate cortex as reported above [7]. Cerebral cortex thickness has not been evaluated previously in either dataset.…”

“…For patients receiving rTMS to the dorsolateral prefrontal cortex (DLPFC) as a treatment for depression, longitudinal studies have shown no global change in brain volume [4], a significant reduction in left hippocampus volume that was driven by the non-responders [5], and a significant increase in hippocampus volume that did not correlate with clinical response [6]. A 2016 study showed a longitudinal increase in gray matter density in several brain areas over a course of rTMS for depression and a single region, the rostral anterior cingulate cortex (rACC) extending into medial prefrontal cortex, with increased gray matter density that correlated with clinical improvement [7]. …”

“…Specifically, we examined whether there were regional changes in cerebral cortex thickness associated with clinical improvement. We hypothesized that cortical thickness would increase in the left DLPFC based on prior research showing regional structural changes at the stimulation site [3], along with increases in cortical thickness at the anterior cingulate in correspondence with clinical improvement, which may correspond to increased gray matter density reported previously [7]. In addition we measured hippocampus volume to evaluate whether nonresponders had decreased hippocampus volume with rTMS treatment, as was reported previously [5] versus hippocampal enlargement, which has been reported recently in association with rTMS treatment for depression [6] and with some consistency with electroconvulsive treatment of depression [8].…”

EFFICACY, SAFETY AND TOLERABILITY OF AUGMENTATIVE rTMS IN TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD): A PROSPECTIVE COHORT STUDY IN CROATIA

“…Four regions in which they detect these changes were: left anterior cingulate cortex, the left insula, left superior temporal gyrus and the right angular gyrus. Increase in the volume of the left anterior cingulate cortex correlated with improvement of depression severity (Lan et al 2016). …”

“…It is believed that rTMS over the DLPFC modulates brain network involved in the regulation of mood and affects various neurotransmitters. Lan and colleagues (2016) described the structural changes in the brain (gray matter volume increased by 3.5-11.2%) in patients with a depressive disorder after rTMS treatment (Lan et al 2016). Four regions in which they detect these changes were: left anterior cingulate cortex, the left insula, left superior temporal gyrus and the right angular gyrus.…”